Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial
Peter B. Gilbert, David C. Montefiori, Adrian B. McDermott, Youyi Fong, David Benkeser, Weiping Deng, Honghong Zhou, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Flora Castellino, Britta Flach, Bob C. Lin, Sarah O’Connell, Charlene McDanal, Amanda Eaton, Marcella Sarzotti‐Kelsoe, Yiwen Lu, Chenchen Yu, Bhavesh Borate, Lars W. P. van der Laan, Nima S. Hejazi, Chuong Huynh, Jacqueline M. Miller, Hana M. El Sahly, Lindsey R. Baden, Mira Baron, Luis de la Cruz‐Merino, Cynthia L. Gay, Spyros A. Kalams, Colleen F. Kelley, Michele P. Andrasik, James G. Kublin, Lawrence Corey, Kathleen M. Neuzil, Lindsay N. Carpp, Rolando Pajón, Dean Follmann, Rubén O. Donis, Richard A. Koup, Immune Assays Team§, Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team§, United States Government (USG)/CoVPN Biostatistics Team§
Abstract
In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.